The case involved a 3-year-old boy who was diagnosed with HLH that had been triggered by a Salmonella infection. Tests later showed that he also had CGD caused by a previously unidentified mutation, which likely increased his risk of developing HLH.
The case, “Hemophagocytic lymphohistiocytosis resulting from a cytokine storm triggered by septicemia in a child with chronic granuloma disease: a case report and literature review,” was reported in the journal BMC Pediatrics.
HLH is a rare and life-threatening disease, in which certain white blood cells — natural killer (NK) and cytotoxic T-cells — damage organs. These cells also collect in the spleen and liver, causing inflammation and swelling there.
CGD is an inherited immune deficiency, in which defects in the NADPH protein and mutations in the CYBB gene make patients more susceptible to infection by bacteria and fungi. Repeated infections increase the risk of developing HLH.
The boy was referred to the Beijing Children’s Hospital in April 2019 with a history of recurrent fever, an enlarged spleen and liver, and low blood cell counts over the previous four weeks.
HLH was diagnosed based on the presence of multiple HLH-2004 diagnosis criteria, including fever, enlarged spleen and liver, low blood counts, high triglycerides, a low fibrinogen count, histological evidence of cells attacking other cells in the bone marrow (a condition called hemophagocytosis), high cytokine counts, and low NK cell activity.
He was prescribed methylprednisolone for his inflammation. Dosing began at 10 mg/kg a day, and was tapered to 1 mg/kg a day at three day intervals over the course of 10 days.
On day three of treatment, blood and bone marrow culture revealed the presence of septicemia, an infection of the blood caused by bacteria, in this case, by Salmonella Typhimurium. The patient was prescribed the anti-infection medication meropenem.
The boy’s signs of septicemia and inflammation improved after a week of anti-infective and anti-inflammatory treatments. At one-month follow-up, there was no recurrence of HLH.
A genetic mutation analysis two weeks after starting treatment revealed the presence of a never-before-reported mutation on one copy of the patient’s CYBB gene, leading to a diagnosis of CGD.
The team noted that treating CGD in the presence of HLH requires caution. The weakened immune systems of CGD children make them more vulnerable to the immunosuppressive therapies that might be used to treat HLH.
Although the boy was not diagnosed with CGD upon admission, his history of repeated infections after birth suggested that he might have a congenital immune deficiency. This prompted his doctors to refrain from giving him intensive chemotherapy.
When CGD is associated with HLH, physicians should choose medications that have weaker immunosuppressive effects, the team advised.
“For patients with recurrent infection in early childhood, we should pay close attention to the possibility of congenital immune deficiency, and genetic testing should be performed as soon as possible,” the researchers wrote.
“On the basis of anti-infection, IVIG [intravenous immunoglobulin] or steroids should be the first choice of HLH treatment, and strong immunosuppressive drugs, such as cyclosporine and etoposide, should be avoided,” they added.